A Single-dose Cross-over Study to Assess Direct and Indirect Effects of Dapagliflozin on Pancreatic Alpha and Beta Cells in Patients With Type 2 Diabetes

NCT ID: NCT02765204

Last Updated: 2016-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2016-12-31

Brief Summary

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The purpose of this study is to evaluate if Dapagliflozin has direct effect on alpha cell glucagon release.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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DS-D-DG

The arm label indicates the order of the given treatments in this crossover designed study (DS=Dapagliflozin and Saxagliptin, D=Dapagliflozin, DG=Dapagliflozin and Glucose).

Group Type EXPERIMENTAL

Dapagliflozin

Intervention Type DRUG

Saxagliptin

Intervention Type DRUG

Glucose

Intervention Type DRUG

DS-DG-D

The arm label indicates the order of the given treatments in this crossover designed study (DS=Dapagliflozin and Saxagliptin, D=Dapagliflozin, DG=Dapagliflozin and Glucose).

Group Type EXPERIMENTAL

Dapagliflozin

Intervention Type DRUG

Saxagliptin

Intervention Type DRUG

Glucose

Intervention Type DRUG

D-DG-DS

The arm label indicates the order of the given treatments in this crossover designed study (DS=Dapagliflozin and Saxagliptin, D=Dapagliflozin, DG=Dapagliflozin and Glucose).

Group Type EXPERIMENTAL

Dapagliflozin

Intervention Type DRUG

Saxagliptin

Intervention Type DRUG

Glucose

Intervention Type DRUG

D-DS-DG

The arm label indicates the order of the given treatments in this crossover designed study (DS=Dapagliflozin and Saxagliptin, D=Dapagliflozin, DG=Dapagliflozin and Glucose).

Group Type EXPERIMENTAL

Dapagliflozin

Intervention Type DRUG

Saxagliptin

Intervention Type DRUG

Glucose

Intervention Type DRUG

DG-D-DS

The arm label indicates the order of the given treatments in this crossover designed study (DS=Dapagliflozin and Saxagliptin, D=Dapagliflozin, DG=Dapagliflozin and Glucose).

Group Type EXPERIMENTAL

Dapagliflozin

Intervention Type DRUG

Saxagliptin

Intervention Type DRUG

Glucose

Intervention Type DRUG

DG-DS-D

The arm label indicates the order of the given treatments in this crossover designed study (DS=Dapagliflozin and Saxagliptin, D=Dapagliflozin, DG=Dapagliflozin and Glucose).

Group Type EXPERIMENTAL

Dapagliflozin

Intervention Type DRUG

Saxagliptin

Intervention Type DRUG

Glucose

Intervention Type DRUG

Interventions

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Dapagliflozin

Intervention Type DRUG

Saxagliptin

Intervention Type DRUG

Glucose

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Males and females aged 18 - 75.
2. Female subjects must meet all of the following criteria:

1. Not breastfeeding
2. Negative pregnancy test result (human chorionic gonadotropin, beta subunit \[hCG\]) at Visit 0 (screening) (not applicable to hysterectomized females).
3. If of childbearing potential (including perimenopausal women who have had a menstrual period within 1 year), must practice and be willing to continue to practice one of the following highly effective birth control methods during the entire duration of the study:

i. Diaphragm or partner use of condom in combination with combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
* Oral
* Intravaginal
* Transdermal ii. Diaphragm or partner use of condom in combination with progestogen-only hormonal contraception associated with inhibition of ovulation:
* Oral
* Injectable
* Implantable iii. Placement of an intrauterine device iv. Placement of an intrauterine hormone-releasing system v. Bilateral tubal occlusion vi. Vasectomised partner (provided that the partner is the sole sexual partner of the female subject and that the vasectomised partner has received medical assessment of the surgical success) vii. Sexual abstinence (defined as refraining from heterosexual intercourse) d) Must practice appropriate birth control as stated above for 10 weeks after the last dose of study medication
3. BMI 20 - 35.
4. Clinical T2D diagnosis at least 6 months prior to enrolment.
5. Metformin treatment, with stable dose for at least 1 month.
6. HbA1c 55 - 86 mmol/mol (7,2-10 % DCCT).

Exclusion Criteria

1. History or sign of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
2. Clinical diagnosis of Type 1 diabetes mellitus and/or history of diabetic ketoacidosis or positive Glutamic Acid Decarboxylase Autoantibodies test (GAD antibodies test).
3. Patients treated with antipsychotics, systemic glucocorticoids, neuropsychiatric stimulants, antidepressants with sympathetic activity, beta blockers or other pharmaceuticals rendering patient unfit for study participation as judged by the investigator.
4. Patients treated with antidiabetic medications other than Metformin.
5. Patients with any other endocrine disease except substituted hypothyroidism.
6. Significant abnormal liver function defined as aspartate aminotransferase (AST) \>3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) \>3x ULN.
7. Patients with impaired liver or kidney function (eGFR \< 60).
8. Known or suspected history of significant drug abuse.
9. History of alcohol abuse or excessive intake of alcohol as judged by investigator.
10. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator.
11. Plasma donation within one month of screening or any blood donation or significant blood loss (\> 400 ml) during the 3 months prior to screening.
12. Any other condition with in the opinion of the investigator would render the patient unsuitable for inclusion in the study and /or for the patients safety.
13. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
14. Judgment by the investigator that the subject should not participate in the study if considers subject unlikely to comply with study procedures, restrictions and requirements.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Uppsala University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jan W Eriksson, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Uppsala University

Locations

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Dept of Medical Sciences Uppsala University Hospital

Uppsala, , Sweden

Site Status

Countries

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Sweden

References

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Lundkvist P, Pereira MJ, Kamble PG, Katsogiannos P, Langkilde AM, Esterline R, Johnsson E, Eriksson JW. Glucagon Levels During Short-Term SGLT2 Inhibition Are Largely Regulated by Glucose Changes in Patients With Type 2 Diabetes. J Clin Endocrinol Metab. 2019 Jan 1;104(1):193-201. doi: 10.1210/jc.2018-00969.

Reference Type DERIVED
PMID: 30137410 (View on PubMed)

Other Identifiers

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2015-005549-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ESR-15-11421

Identifier Type: -

Identifier Source: org_study_id